: Premenstrual Dysphoric disorder (PMDD) is widely recognized as a recurrent disorder related to hormonal variations of the menstrual cycle. PMDD shares many of the features of depression anxiety and the dysphoric states. Whereas alterations in calcium homeostasis have long been associated with many affective disturbances, recent evidence has suggested that luteal phase symptomatology may be associated with a perturbation in calcium homeostasis. Recently reported abnormalities in calciotropic hormone regulation, as well as the beneficial response to calcium treatment, all support the hypothesis that disordered calciotropic hormone regulation is a major provocative factor in luteal phase symptomatology. The purpose of the investigation is to understand more completely the extent to which calcium regulation is disturbed in PMDD by utilizing new tools to assess calcium and bone turnover. This investigation seeks to confirm our preliminary data in a definitive study. The long-term objective is to elucidate the pathophysiology of PMDD as it relates to the calciotropic hormones and bone markers. The experimental design involves enrolling 70 with PMDD and 35 controls. Following 2 months of baseline symptom documentation, women with PMDD and controls will be enrolled in a 1-month observational period with frequent hormonal samplings, urinary collections and daily ratings. Clinical evaluation will involve a detailed history and physical examination, a structured psychiatric interview and a dietary assessment. Hormonal evaluation will include total and ionized calcium intact parathyroid hormone, 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D, estradiol, progesterone, osteocalcin, urinary N-telopeptide, IGF-1 and TNF-A. Each subjects will be initially screened prospectively for 2 menstrual cycles with a daily, self assessment scale; symptoms will then be monitored and quantified for another 1 month while undergoing blood and urine sampling. The observation period will provide extensive characterization of the calciotropic hormones and biochemical markers of bone turnover across the menstrual cycle with simultaneous symptom ratings in women with PMDD and controls. Bone density evaluation will be performed as well on all subjects. Understanding the pathophysiology associated with PMDD may lead to effective therapeutic strategies to prevent the neuropsychiatric disturbances and abnormal calcium regulation that are characteristic of this disorder.